It's been an interesting time here in San Francisco at the American Urology Association (AUA) meeting. Mostly, I've attended prostate cancer sessions to get both a breadth and depth perception of what's going on this cancer type.
My focus is very much therapeutic development, so here are three key trends that I've noticed at the 2010 AUA meeting:
- PSA is not a brilliant biomarker, but it's all we have for now.
- Androgen ablation is not permanent.
- Immunotherapy is a hot new topic.
What alternatives are there to PSA?
An abstract today from the Colorado Cancer Center suggested that PCA3 may offer a urine based genetic assay for detection of prostate cancer in men with elevated levels of PSA. PSA can offer false positive results and up to 75% men with prostate cancer have a negative biopsy. This new approach sounds promising. PCA3 is overexpressed in more than 90 percent of prostate cancers and the gene overexpression is specific to prostate cancer. It has been linked to more accurate prediction of positive biopsies compared to PSA, and it is easy to test in urine samples following a digital rectal exam of the prostate.
Presumably it may turn out to be more accurate than PSA and perhaps offer a better way to detect either the actual disease earlier or more aggressive disease earlier. The test was developed by GenProbe and is not yet approved by the FDA, but a new test to watch out for.
Androgen ablation therapies are not particular effective
Often times, testosterone levels rise above the minimum castrate level after about a year. Ultimately, more effective androgen receptor antagonists are needed, hence the significant interest in this meeting in abiraterone and MDV3100, two new antagonists in phase III development. Long term use of androgen deprivation is also inevitably associated with side effects, which have not been well appreciated until recently.
The approval of Provenge gives hope that survival can be extended without drastic side effects
Pharma companies in the oncology space would do well to realise that sick people with cancer don't want to be reminded of such and most certainly do not want a 'relationship' with a brand. This is not Nike or a FMCG brand offering coupons and offers. What most people do want is less side effects and better efficacy without having to trade them off.
Now that we have a proof of concept poster child in Provenge in a solid tumour, we can also see that it may ultimately offer a way to combine newer hormonal therapies with a vaccine to offer men a more effective tool against their disease, delaying the time not only to progression, but also to metastases and chemotherapy.
Other immunotherapies are also being evaluated in prostate cancer, including ipilimumab (BMS), an anti-CTLA4 inhibitor and ProstVac, a cancer vaccine. More on ipilimumab in another blog post but having had a few queries as to what ProstVac is, here's my basic take on it.
ProstVac differs from Provenge in that it requires 7 infusions over a 6 month period as opposed to 3 within the first month. My understanding is that it is a sequentially dosed combination of two different Poxviruses which each encode prostate specific antigen (PSA) plus three immune enhancing co-stimulatory molecules, B7.1, ICAM-1, and Lfa-3 (TRICOM). The first Poxvirus is Vaccinia-PSA-TRICOM, which is replication competent and is good for immune priming. The second Poxvirus is Fowlpox-PSA-TRICOM, a non-replicating virus, which is good for repetitive immune boosting. In some ways, it seeks to achieve the same end as Provenge (T-cell stimulation) but via a slightly different approach.
More on prostate cancer at the American Society of Clinical Oncology (ASCO) meeting next week!